Kolbe–Schmitt reaction

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Kolbe–Schmitt reaction
Named after
Reaction type Addition reaction
Identifiers
Organic Chemistry Portal kolbe-schmitt-reaction
RSC ontology ID RXNO:0000182

The Kolbe–Schmitt reaction or Kolbe process (named after Hermann Kolbe and Rudolf Schmitt) is a carboxylation chemical reaction that proceeds by treating phenol with sodium hydroxide to form sodium phenoxide, [1] then heating sodium phenoxide with carbon dioxide under pressure (100 atm, 125 °C), then treating the product with sulfuric acid. The final product is an aromatic hydroxy acid which is also known as salicylic acid (the precursor to aspirin). [2] [3] [4] [5]

The Kolbe-Schmitt reaction Kolbe-Schmitt.png
The Kolbe–Schmitt reaction

By using potassium hydroxide, 4-hydroxybenzoic acid is accessible, an important precursor for the versatile paraben class of biocides used e.g. in personal care products.

The methodology is also used in the industrial synthesis of 3-hydroxy-2-naphthoic acid; the regiochemistry of the carboxylation in this case is sensitive to temperature. [6]

Reaction mechanism

The Kolbe–Schmitt reaction proceeds via the nucleophilic addition of a phenoxide, classically sodium phenoxide (NaOC6H5), to carbon dioxide to give the salicylate. The final step is the reaction (protonation) of the salicylate anion with an acid to form the desired salicylic acids (ortho- and para- isomers).

Kolbe-Schmitt reaction Kolbe-Schmitt-reaction-mechanism.png
Kolbe–Schmitt reaction

Related Research Articles

<span class="mw-page-title-main">Hermann Kolbe</span> German chemist (1818–1884)

Adolph Wilhelm Hermann Kolbe was a major contributor to the birth of modern organic chemistry. He was a professor at Marburg and Leipzig. Kolbe was the first to apply the term synthesis in a chemical context, and contributed to the philosophical demise of vitalism through synthesis of the organic substance acetic acid from carbon disulfide, and also contributed to the development of structural theory. This was done via modifications to the idea of "radicals" and accurate prediction of the existence of secondary and tertiary alcohols, and to the emerging array of organic reactions through his Kolbe electrolysis of carboxylate salts, the Kolbe-Schmitt reaction in the preparation of aspirin and the Kolbe nitrile synthesis. After studies with Wöhler and Bunsen, Kolbe was involved with the early internationalization of chemistry through work in London. He was elected to the Royal Swedish Academy of Sciences, and won the Royal Society of London's Davy Medal in the year of his death. Despite these accomplishments and his training important members of the next generation of chemists, Kolbe is best remembered for editing the Journal für Praktische Chemie for more than a decade, in which his vituperative essays on Kekulé's structure of benzene, van't Hoff's theory on the origin of chirality and Baeyer's reforms of nomenclature were personally critical and linguistically violent. Kolbe died of a heart attack in Leipzig at age 66, six years after the death of his wife, Charlotte. He was survived by four children.

<span class="mw-page-title-main">Salicylic acid</span> Chemical compound used in medicines and industry

Salicylic acid is an organic compound with the formula HOC6H4COOH. A colorless, bitter-tasting solid, it is a precursor to and a metabolite of aspirin (acetylsalicylic acid). It is a plant hormone, and has been listed by the EPA Toxic Substances Control Act (TSCA) Chemical Substance Inventory as an experimental teratogen. The name is from Latin salix for willow tree, from which it was initially identified and derived. It is an ingredient in some anti-acne products. Salts and esters of salicylic acid are known as salicylates.

<span class="mw-page-title-main">Quinoline</span> Chemical compound

Quinoline is a heterocyclic aromatic organic compound with the chemical formula C9H7N. It is a colorless hygroscopic liquid with a strong odor. Aged samples, especially if exposed to light, become yellow and later brown. Quinoline is only slightly soluble in cold water but dissolves readily in hot water and most organic solvents. Quinoline itself has few applications, but many of its derivatives are useful in diverse applications. A prominent example is quinine, an alkaloid found in plants. Over 200 biologically active quinoline and quinazoline alkaloids are identified. 4-Hydroxy-2-alkylquinolines (HAQs) are involved in antibiotic resistance.

The Hofmann rearrangement is the organic reaction of a primary amide to a primary amine with one less carbon atom. The reaction involves oxidation of the nitrogen followed by rearrangement of the carbonyl and nitrogen to give an isocyanate intermediate. The reaction can form a wide range of products, including alkyl and aryl amines.

The Kolbe electrolysis or Kolbe reaction is an organic reaction named after Hermann Kolbe. The Kolbe reaction is formally a decarboxylative dimerisation of two carboxylic acids. The overall reaction is:

The Cannizzaro reaction, named after its discoverer Stanislao Cannizzaro, is a chemical reaction which involves the base-induced disproportionation of two molecules of a non-enolizable aldehyde to give a primary alcohol and a carboxylic acid.

<span class="mw-page-title-main">Benzoin (organic compound)</span> Chemical compound

Benzoin ( or ) is an organic compound with the formula PhCH(OH)C(O)Ph. It is a hydroxy ketone attached to two phenyl groups. It appears as off-white crystals, with a light camphor-like odor. Benzoin is synthesized from benzaldehyde in the benzoin condensation. It is chiral and it exists as a pair of enantiomers: (R)-benzoin and (S)-benzoin.

Dichlorocarbene is the reactive intermediate with chemical formula CCl2. Although this chemical species has not been isolated, it is a common intermediate in organic chemistry, being generated from chloroform. This bent diamagnetic molecule rapidly inserts into other bonds.

<span class="mw-page-title-main">Wilhelm Rudolph Fittig</span> German chemist (1835–1910)

Wilhelm Rudolph Fittig was a German chemist. He discovered the pinacol coupling reaction, mesitylene, diacetyl and biphenyl. Fittig studied the action of sodium on ketones and hydrocarbons. He discovered the Fittig reaction or Wurtz–Fittig reaction for the synthesis of alkylbenzenes, he proposed a diketone structure for benzoquinone and isolated phenanthrene from coal tar. He discovered and synthesized the first lactones and investigated structures of piperine, naphthalene, and fluorene.

The Strecker amino acid synthesis, also known simply as the Strecker synthesis, is a method for the synthesis of amino acids by the reaction of an aldehyde with cyanide in the presence of ammonia. The condensation reaction yields an α-aminonitrile, which is subsequently hydrolyzed to give the desired amino acid. The method is used for the commercial production of racemic methionine from methional.

<span class="mw-page-title-main">Reimer–Tiemann reaction</span> Chemical reaction for ortho-formylation of phenols

The Reimer–Tiemann reaction is a chemical reaction used for the ortho-formylation of phenols. with the simplest example being the conversion of phenol to salicylaldehyde. The reaction was first reported by Karl Reimer and Ferdinand Tiemann.

<span class="mw-page-title-main">Mandelic acid</span> Chemical compound

Mandelic acid is an aromatic alpha hydroxy acid with the molecular formula C6H5CH(OH)CO2H. It is a white crystalline solid that is soluble in water and polar organic solvents. It is a useful precursor to various drugs. The molecule is chiral. The racemic mixture is known as paramandelic acid.

The Letts nitrile synthesis is a chemical reaction of aromatic carboxylic acids with metal thiocyanates to form nitriles. The reaction includes the loss of carbon dioxide and potassium hydrosulfide. The polar basic substitution reaction was discovered in 1872 by Edmund A. Letts.

<span class="mw-page-title-main">Phenyl salicylate</span> Chemical compound

Phenyl salicylate, or salol, is the organic compound with the formula C6H5O2C6H4OH. It is a white solid. It is occasionally used in sunscreens and as an antiseptic.

Carboxylation is a chemical reaction in which a carboxylic acid is produced by treating a substrate with carbon dioxide. The opposite reaction is decarboxylation. In chemistry, the term carbonation is sometimes used synonymously with carboxylation, especially when applied to the reaction of carbanionic reagents with CO2. More generally, carbonation usually describes the production of carbonates.

<span class="mw-page-title-main">Sodium phenoxide</span> Chemical Compound

Sodium phenoxide (sodium phenolate) is an organic compound with the formula NaOC6H5. It is a white crystalline solid. Its anion, phenoxide, also known as phenolate, is the conjugate base of phenol. It is used as a precursor to many other organic compounds, such as aryl ethers.

<span class="mw-page-title-main">Phenolates</span>

Phenolates are anions, salts, and esters of phenols, containing the phenolate ion. They may be formed by reaction of phenols with strong base.

In organic chemistry, ketonic decarboxylation is a type of organic reaction and a decarboxylation converting two equivalents of a carboxylic acid to a symmetric ketone by the application of heat. It can be thought of as a decarboxylative Claisen condensation of two identical molecules. Water and carbon dioxide are byproducts:

<span class="mw-page-title-main">Carbyl sulfate</span> Chemical compound

Carbyl sulfate is an organosulfur compound. The white solid is the product of the reaction of sulfur trioxide and ethylene. It is used in preparation of some dyes and other organosulfur compounds. Carbyl sulfate is a colorless, crystalline, hygroscopic substance although commercial product can appear as a liquid. Because of its unpleasant properties carbyl sulfate is difficult to handle and is usually not isolated but further processed to give secondary products.

In organic chemistry, alkynylation is an addition reaction in which a terminal alkyne is added to a carbonyl group to form an α-alkynyl alcohol.

References

  1. C. S. Marvel; A. L. Tanenbaum (1929). "γ-Phenoxypropyl Bromide". Org. Synth. 9: 72. doi:10.15227/orgsyn.009.0072.
  2. Hermann Kolbe (1860). "Ueber Synthese der Salicylsäure" [On the synthesis of salicylic acid]. Annalen der Chemie und Pharmacie . 113 (1): 125–127. doi:10.1002/jlac.18601130120.
  3. R. Schmitt (1885). "Beitrag zur Kenntniss der Kolbe'schen Salicylsäure Synthese" [Contribution to [our] knowledge of Kolbe's synthesis of salicylic acid]. Journal für Praktische Chemie . 2nd series. 31 (1): 397–411. doi:10.1002/prac.18850310130.
  4. A. S. Lindsey and H. Jeskey (1957). "The Kolbe-Schmitt Reaction". Chem. Rev. 57 (4): 583–620. doi:10.1021/cr50016a001. (Review)
  5. R. T. Morrison and R. N. Boyd (1983). Organic Chemistry (4th ed.). Allyn and Bacon. p.  976-7. ISBN   0-205-05838-8.
  6. Gerald Booth (2005). "Naphthalene Derivatives". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a17_009. ISBN   3-527-30673-0..